Rapamycin reduces cervical cancer cells viability in hypoxic condition: Investigation of the role of autophagy and apoptosis

Abstract

Background: Rapamycin has been known as an anti-cancer agent that affects different malignancies such as glioblastoma and prostate cancer. However, there are few studies concerning rapamycin effects on the cervical cancer cells. In this study, it was aimed to investigate the possible effect of rapamycin on a cervical cancer cell line and explored the possible mechanism(s) and pathway(s) for this agent. Materials and Methods: To do so, HeLa cells as cervical cancer cell line were used and treated with different concentrations of rapamycin under both normoxic and hypoxic condi-tions. Then, cell viability assays, Western blot, quantitative real-time polymerase chain reaction (QR-PCR), acridine orange and acridine orange/propidium iodide staining were performed to evaluate rapamycin effect on the mentioned cell line. Results: The results showed that autophagy and apoptosis-related genes increased significantly in rapamycin-treated HeLa cells compared to controls. Moreover, cervical cancer cell death by rapamycin-induced autophagy in hypoxia was greater than normoxia compared with controls. In this study, it was showed that autophagy induction by rapamycin can mediate programmed cell death of cervical cancer cells, especially in hypoxic condition. Conclusion: These findings provide a new evidence that rapamycin may inhibit hypoxic HeLa cell proliferation through the trigger of programmed cell death, facilitating the development of novel anti-cancer therapy.